Tissue inplant systems and methods for sustaining viable high cell densities within a host

Abstract

Implant assemblies and methodologies provide immuno-protection for implanted allografts, xenografts, and isografts. The assemblies and methodologies establish a boundary between the host and the implanted cells. The boundary has a pore size, an ultimate strength, and a metabolic transit value that assures the survival of the cells during the critical ischemic period and afterward. The boundary allows the fabrication and clinical use of implant assemblies and methodologies that can carry enough cells to be of therapeutic value to the host, yet occupy a relatively small, compact area within the host.

We claim: 
     
       1. An assembly for embedding in host tissue, where it is exposed to physiological stresses and vascularization by host tissue comprising wall means defining a chamber for holding cells while embedded in host tissue, the wall means including means for forming a porous boundary between host tissue and the cells in the chamber, the porous boundary being characterized by a tensile strength and a pore size sufficient to isolate the implanted cells from an immune response of host tissue in which the chamber is embedded; and   a metabolic transit value including a permeability value of greater than about 1.5×10 -4  cm/sec. for  125  I-labeled insulin as determined by pseudo-steady state diffusion in a diaphragm cell,     whereby the wall means sustains a flux of nutrients from host tissue in which the chamber is embedded to the cells in the chamber and waste products from the cells in the chamber to host tissue in which the chamber is embedded in the absence of close vascular structures to thereby sustain viability of the cells in the chamber until vascular structures of host tissue form close to the porous boundary.   
     
     
       2. An assembly according to claim 1 and further including an angiogenic material that, when embedded in host tissue, stimulates the growth of vascular structures by host tissue in which the chamber is embedded close to the boundary.   
     
     
       3. An assembly according to claim 1 or 2 and further including a second material that overlies the porous boundary and forms an interface with host tissue in which the chamber is embedded, the second material having a structural conformation that, when embedded in host tissue, supports the growth of vascular structures by host tissue close to the boundary.   
     
     
       4. An assembly according to claim 1 or 2 wherein the pore size blocks the passage of molecular immunogenic factors from host tissue to the cells in the chamber.   
     
     
       5. An assembly according to claim 1 or 2 wherein the pore size blocks the passage of inflammatory cells from host tissue to the cells in the chamber.   
     
     
       6. An assembly according to claim 1 wherein the metabolic transit value includes a porosity value that is greater than about 15%, wherein the porosity value represents the volume in the porous boundary occupied by pores, expressed as a percentage of the total volume of the porous boundary.   
     
     
       7. An assembly according to claim 1 or 2 wherein the chamber contains a given number of cells (N),   wherein the porous boundary covers a given area (A), and   wherein A/N is less than about 200 μm 2  /cell.   
     
     
       8. An assembly according to claim 1 or 2 wherein the tensile strength is greater than about 100 pounds per square inch (PSI).   
     
     
       9. A method of implanting cells comprising the steps of surrounding at least a portion of the implanted cells with a porous boundary that has a tensile strength and a pore size sufficient to isolate the implanted cells from an immune response of host tissue; and a metabolic transit value including a permeability value of greater than about 1.5×10 -4  cm/sec. for  125  I-labeled insulin as determined by pseudo-steady state diffusion in a diaphragm cell, and   embedding the porous boundary within host tissue   whereby the porous boundary sustains a flux of nutrients from host tissue to the cells within the boundary and waste products from the cells within the boundary to host tissue in which the boundary is embedded sufficient to maintain viability of the cells within the boundary until vascular structures of host tissue form close to the boundary.   
     
     
       10. A method according to claim 9 and further including the step of exposing the boundary to an angiogenic substance that stimulates the formation of vascular structures by host tissue close to the boundary. 
     
     
       11. A method according to claim 9 or 10 and further including the step of, before embedding the boundary in host tissue, overlaying on the boundary a second material that has a structural conformation that supports the growth of vascular structures by host tissue close to the boundary.